Summary: The short average service life of current dental composite restorative systems and increasing occurrence of secondary caries adjacent to composite restorations and sealants are necessitating the development of new, longer lasting dental materials having novel monomers and polymers, reinforcing fillers, and adhesive components. The goal of this proposed research is to develop novel dental composite systems, for use in restorations, sealants, and other dental services that are superior in properties and endurance to currently used Bis-GMA/TEGDMA and urethane-dimethacrylate systems. We will design and produce new monomers and their polymers that are not susceptible to enzymatic or hydrolytic degradation, establish a self- healing technique to significantly extend the fatigue life of these composites, and formulate smart antibacterial components which are activated in the oral environment only when needed. We propose three specific aims that target these three key developments. In Specific Aim 1, we propose to improve durability by replacing the hydrolyzable ester groups, contained in current polymers and bonding agents, with hydrolytically stable ether groups in the corresponding polymers and bonding agents. In Specific Aim 2, we will develop self-healing dental composites (SHDC) that will autonomously repair micro-cracks that are hard to detect and almost impossible to repair clinically. Autonomic self-healing will significantly improve the durability of these materials by preventing catastrophic failures caused by thermal and mechanical challenges encountered in the oral environment. In Specific Aim 3, we propose to build a self-defense capability for the systems by incorporating nanoparticles functionalized with novel coupling agents that will release antimicrobial components only when exposed to bacterial attack or hydrolytic degradation. The integrity and durability of these novel systems will be compared with Bis-GMA/TEGDMA based commercial systems under challenges like those that occur in the oral environment, including cariogenic biofilms, enzymatic degradations, thermal cycling fatigue and mechanical cycling fatigue. We expect that the novel materials, having features achieved by these three specific aims, will significantly surpass the performances of current Bis-GMA-TEGDMA-based commercial materials under these challenges. It is thus predictable that the new system will provide a significantly extended service life, at least by a factor of two. All of the features in the new system can be easily integrated into other restorative systems developed by the awardees of this U01-RFA, and can be used in composites and their dental adhesives. We plan to share our data and resources and collaborate with the awardees by way of all feasible procedure to achieve the goals of this program.